Brachytherapy and Fertility
Sir,
We are pleased to report our first case of paternity after prostate brachytherapy; we have treated ≈ 600 men with low-dose rate 125I-interstitial brachytherapy since 1999. The father of our first (and to date only) child presented in 2001, aged 61 years, with early organ-confined prostate cancer, stage T2c, a PSA level of 4.4 ng/mL and Gleason sum 5 cancer. He received brachytherapy as monotherapy on 21 June 2001. In 2004, 40 months after treatment, his wife gave birth to a boy. The child was born fit and well with no evidence of any birth anomalies.
A literature search shows little or no information on fertility after brachytherapy, or any associated risk of birth defects, probably partly reflecting that prostate cancer tends to present in older men who have usually completed their families. However, as a result of PSA screening, patients are presenting earlier and younger, and fertility is becoming more of an issue. We found one paper by Mydlo et al.[1]. reporting the birth of three children to patients who had received prostate brachytherapy. In the current BJU Int Grocela et al.[2]. report two births in a series of 485 patients. Semen analysis on the two men confirmed viable sperm with normal morphology in a low ejaculatory volume.
It is understood that external beam radiotherapy can reduce spermatogenesis both as a result of a direct effect on spermatagonia, causing increased levels of FSH due to negative feedback on the pituitary, and as a result of Leydig cell dysfunction, with a resultant reduction in serum testosterone levels.
Doses of <0.2 Gy have been reported to have no effect on FSH levels or spermatogenesis, with doses of 0.2–0.7 Gy causing a transient rise in FSH and a reduction in sperm count, with recovery within 12–24 months. Doses of >1.2 Gy are associated with a reduced chance of recovery, and doses of >2 Gy are likely to cause permanent infertility [3]. This is supported by data from Greiner [4], who reported complete recovery of spermatogenesis within 14–22 months in a series of patients who received a dose of <1 Gy to the testes from radiation of the pelvic and inguinal nodes to treat seminoma. The Norwegian birth register identifies 95 children born to 69 of 430 patients irradiated for testicular cancer (para-aortic nodes 0.09 Gy, with or without iliac and inguinal nodes, 0.32 Gy [5]). These children were born at 10–122 months after irradiation. There was no increase in the frequency of malformations or differences in median height or weight compared to normal births [6]. Doses required to stop testosterone production from Leydig cells are much higher, at >20 Gy [7].
It was calculated that the dose received by the testes from 125I-prostate brachytherapy is ≈ 0.18 Gy [1]; given the evidence, this is too low to affect spermatogenesis or testosterone levels, but fertility also depends on the delivery of the spermatagonia, which relies on the seminal fluid. The base of the seminal vesicles are included in the radiation volume and patients often notice a change in their ejaculate.
There are concern about the risk of congenital deformity secondary to non-lethal mutations. The radiobiological dose of 125I is delivered over ≈ 120 days (4 months), calculated using dose rate, activity and the half-life of 125I. After this period the radiation emitted is very low and the dose to the testes probably negligible. The process of spermatogenesis takes 74 days. We recommend that our patients should not try to conceive within 1 year of treatment, to reduce any potential risk of malformations.
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